Regulatory Elements of Neurotransmitter-Specific Genes

Loer, Curtis

Abstract

To function correctly in the nervous system, a neuron must produce an appropriate neurotransmitter. Little is known about the mechanisms that govern this choice within developing neurons. Since the same neurotransmitters are used by organisms throughout the animal kingdom, genes regulating neurotransmitter choice are likely to be conserved among simple and complex organisms. Therefore, it is proposed to study this problem in a simple organism which is readily amenable to genetic and molecular analysis, the nematode worm Caenorhabditis elegans. This study will examine the regulation of neurotransmitter-specific genes expressed in serotonergic neurons ('serotonergic marker genes') of C. elegans. C. elegans genes necessary for serotonin synthesis and packaging: tryptophan hydroxylase, dopa decarboxylase, and vesicular monoamine transporter have been identified. It is proposed to 1) identify regulatory elements by comparing promoters of the homologous marker genes from a closely-related species and performing promoter deletion analyses, 2) identify regulatory genes by screening for mutants that do not express or mis-express the serotonergic marker genes. The long term goal of these studies is to understand how genes control the expression of specific neuronal identities, in particular, the neurotransmitter type of a neuron. Such studies may allow us to understand better why neurological disorders target specific subsets of neurons and ultimately to develop therapies to control the expression of neurotransmitters in specific cells of the human nervous system.